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Home , Biopolymer, Pyrrolysine, Selenocysteine

Chapter 25: Amino Acids, , and . unit: α-amino acids

H NH2 R = sidechain R CO2H α- Biopolymer: the monomeric amino acids are linked through an bond (the carboxylic acids of one AA with the α-amino group of a second)

R R1 R 1 H + 2 - H2O N CO2 H3N CO2 H3N H3N CO2 C-terminus O R N-terminus 2

O R O R O R O H 2 H 4 H 6 H N N N N N N N N H H H H R1 O R3 O R5 O R7 or (polypeptide)

peptide (< 50 amino acids)

protein (> 50 amino acids) 323

25.1: Classification of Amino Acids. AA’s are classified according to the location of the amino group. H H H H H H H2N C CO2H H2N C C CO2H H2N C CC CO2H H H H H H H α-amino acid β-amino acid γ-amino acid (2-amino ) (3-amino carboxylic acid) (4-amino carboxylic acid)

There are 20 genetically encoded α-amino acids found in peptides and proteins (Table 20.1, p. 1032-3)

19 are primary , 1 () is a secondary 19 are “chiral”, 1 () is achiral; the natural configuration of the α-carbon is L. (Ch. 25.2) CHO CHO CO2H CO2H H OH HO H H2N H H2N H CH OH CH OH 2 2 CH3 R D- L-glyceraldehyde L-

CHO CHO CO2H CO2H HO H H OH H2N H H2N H H OH HO H H OH H3C H

CH2OH CH2OH CH3 CH2CH3 324 D-erythrose L-erythrose L-theronine L- (2S,3R) (2S,3S)

149 α-Amino acids are classified by the properties of their sidechains. Nonpolar (hydrophobic):

– COO COO– COO– NH 3 NH3 NH3 Glycine (Gly, G) (S)-(+)-Alanine (Ala, A) (S)-(+)- (Val, V)

– S COO– COO COO–

NH3 NH3 NH3 (S)-(–)- (Leu, L) (2S,3S)-(+)-Isoleucine (Ile, I) (S)-(–)- (Met, M)

COO– COO– N COO– NH H H 3 N NH3 H (S)-(–)-Proline (Pro, P) (S)-(–)- (Phe, F) (S)-(–)- (Trp, W) Polar but non-ionizable: OH COO– COO– HO COO– NH3 NH3 HO NH3 (S)-(–)- (Ser, S) (2S,3R)-(–)- (Thr, T) (S)-(–)- (Tyr, Y) pKa ~ 13 pKa ~ 13 pKa ~ 10.1

– COO H N COO– O HS 2 COO– NH3 O NH3 H2N NH3 (R)-(–)- (Cys, C) (S)-(–)- (Asn, N) 325 (S)-(+)- (Gln, Q) pKa ~ 8.2

O Acidic: - – O COO COO– -O O NH3 NH3 (S)-(+)- (Asp, D) (S)-(+)- (Glu, E) pKa ~ 3.6 pKa ~ 4.2

Basic: N H H – – N H3N COO H COO COO– NH H N N NH3 N 3 2 H NH H 3 (S)-(+)- (Lys, K) (S)-(–)- (His, H) (S)-(+)- (Arg, R) pKa ~ 10.5 pKa ~ 6.0 pKa ~ 12.5 Non-standard (but genetically encoded): N COO – H – HSe N COO +NH H 3 O +NH3 (R)- (Sec, U) (Pyl, O)

25.2: Stereochemistry of Amino Acids: The natural configuration of the α-carbon is L. D-Amino acids are found in the cell walls of . The D-amino acids are not genetically encoded, but derived from the epimerization of L-isomers (Ch. 25.6). 326

150 25.3: Acid-Base Behavior of Amino Acids. Amino acids exist as a zwitterion: a dipolar ion having both a formal positive and formal negative charge (overall charge neutral).

R R + _ H2N CO2H H3N CO2 H H

pKa ~ 5 pKa ~ 9 Amino acids are amphoteric: they can react as either an acid or a base. Ammonium ion acts as an acid, the carboxylate as a base.

Isoelectric point (pI): The pH at which the amino acid exists largely in a neutral, zwitterionic form (influenced by the nature of the sidechain)

_ R + R + H3O R HO _ H N CO H + _ H N CO 3 2 H N CO 2 2 3 2 H H pKa 1 H pKa2 low pH high pH

Table 25.2 (p. 1037) & 25.3 (p. 1038) 327

Bronsted Acid: proton donor (H+) weak acids (and bases) do not fully dissociate

+ − H-A + H2O H3O + A

+ − ______[H3O ] [A ] Ka = [H-A] acid dissociation constant

pKa = -log Ka

pH = -log [H+]

Henderson-Hasselbalch Equation: Relates pKa with pH

[A−] pH = pK + log ______a [H-A]

− when [A ] = [H-A], the pH = pKa

For a review see: http://themedicalbiochemistrypage.org/ 328

151 H H H

H3N CO2H H3N CO2 H2N CO2 H pKa1 ~ 2.3 H pKa2 ~ 9.6 H pI ~ 6.0

NH NH NH NH HN HN N N • pI = 7.6

CH2 CH2 CH2 pKa2 ~ 9.2 CH2 pKa1 ~ 1.8 pKa3 ~ 6.0 H3N CO2H H3N CO2 H3N CO2 H2N CO2 H H H H pI ~ 7.6

329

pKa + pKa pI = x y 2

CH CH + 3 + CH3 3 H N CO H H N CO pKa1 + pKa2 3 2 H3N CO2 2 2 pI = pKa H H 1 H pKa2 2 (2.3) (9.7) low pH high pH pI = 6.0

CO H 2 CO2H CO2 CO2

CH2 CH CH2 CH 2 2 pKa1 + pKa3 H3N CO2H pKa H3N CO2 H3N CO2 H2N CO2 pI = 1 pKa3 pKa 2 H H 2 (1.9) H (3.6) (9.6) H low pH high pH pI = 2.7

NH3 NH NH3 NH3 2 (CH2)4 (CH ) (CH ) (CH2)4 pKa + pKa 2 4 2 4 pI = 2 3 H3N CO2H H N CO H N CO H2N CO2 pKa1 3 2 pKa 2 2 pKa3 2 2 H H (2.2) H (9.0) H (10.5) low pH high pH pI = 9.7

330

152 Electrophoresis: separation of polar compounds based on their mobility through a solid support. The separation is based on charge (pI) or molecular mass. (Fig. 25.2, p. 1039)

+ _

+ _ ____ + + + +

331

25.4: Synthesis of Amino Acids:

Br NH2 Br2, PBr3 NH3 R-CH2-CO2H R C CO2H RC CO2H Ch. 20.1 Ch. 20.15 H H Strecker Synthesis: recall reductive amination (Ch. 21.10) and cyanohydrin formation (Ch. 17.7)

NaB(CN)H3 NH2 O NH3 NH2 RC CO2H R C CO2H R C CO2H H H

NH NH O NaC≡N 2 H O+ 2 NH3 NH2 3 RC C≡N R C CO2H R CH R CH -or- H NaOH, H2O H N≡C: Amidomalonate Synthesis: recall the malonic acid synthesis (Ch. 20.6) O O

H O 2N HH HN CO Et EtO Na HN CO Et 3 2 2 C C C - CO2 RCH CO H H CO Et RCH2X RCH CO Et 2 2 2 2 2 332

153 25.5: Reactions of Amino Acids. Amino acids will undergo reactions characteristic of the amino (amide formation) and carboxylic acid (ester formation) groups.

H3C O O O H2N H H N HN HOCH2CH3 3 H H3CO CH3 H R CO CH CH + base 2 2 3 H R CO2 R CO2H

25.6: Some Biochemical Reactions of Amino Acids. Many involved in amino acid biosynthesis, metabolism and catabolism are (vitamin B6, PLP) dependent.

(please read) - R CO2 O H racemase, - H CO2 R - N R CO2 epimerase H 2- OH + O3PO NH OH NH3 3 PO N N D-amino acid L-amino acid pyridoxal H decarboxylase phosphate (PLP) R H transaminase H Mechanism 25.1 (p.1044) - H3N R CO2 O 333 Mechanism 25.2 (p.1047-8)

25.7: Peptides. Proteins and peptides are made up of amino acid units (residues) that are linked together through the formation of amide bonds (peptide bonds) from the amino group of one residue and the carboxylate of a second residue

HO H + - H2O N CO2H H2N CO2H H2N H2N CO2H C-terminus O N-terminus Alanine Serine OH Ala - Ser - H2O (A - S) HO H C-terminus By convention, peptide sequences N CO H H N 2 N-terminus 2 are written left to right from the O Ser - Ala N-terminus to the C-terminus (S - A)

O R O R O R O H 2 H 4 H 6 H N N N N N N N N backbone H H H H R1 O R3 O R5 O R7 334

154 The amide (peptide) bond has C=N double bond character due to resonance resulting in a planar geometry _ O R2 O R H H H 2 H N N N + N N N restricts rotations R H O 1 R1 H O resistant to hydrolysis amide bond The N-H bond of one amide linkage can form a hydrogen bond with the C=O of another. O H N R N-O distance 2.85 - 3.20 Å N H O N H O N H O R R H N H N optimal N-H-O angle is 180 ° O O Disulfide bonds: the thiol groups of cysteine can be oxidized to form disulfides (Cys-S-S-Cys) (Ch. 15.2)

NH2 1/2 O2 H2O NH2 S CO H 2 2 SH HO2C S HO2C NH H2 2

R9 O R11 O R13 R6 O R8 O R10 H H H H H H N N N N N N N N N N N N H H H H H H O O R12 O O O R9 O S HS 1/2 O2 SH S R O O R H R1 O O R5 1 H H 5 H 2 H H H N N N N N N 335 N N N N N N H H H H H H O R O R O O R2 O R4 O 2 4

25.8: Introduction to Peptide Structure Determination. Protein Structure: primary (1°) structure: the amino acid sequence secondary (2°): frequently occurring substructures or folds tertiary (3°): three-dimensional arrangement of all atoms in a single polypeptide chain quaternary (4°): overall organization of non-covalently linked subunits of a functional protein.

1. Determine the amino acids present and their relative ratios 2. Cleave the peptide or protein into smaller peptide fragments and determine their sequences 3. Cleave the peptide or protein by another method and determine their sequences. Align the sequences of the peptide fragments from the two methods

336

155 25.9: Amino Acid Analysis. automated method to determine the amino acid content of a peptide or protein

Reaction of primary amines with ninhydrin O O O NH3 + RCHO + CO + O N 2 R CO2 O O O Ninhydrin Enzymatic peptide [H] reduce any digestion -or- disulfide NH3 individual -or- amino acids protein bonds + R CO2 H3O , Δ

liquid derivatize w/ Detected w/ chromatography ninhydrin UV-vis

Different amino acids have different 1972 Nobel Prize in Chemistry chromatographic William Stein mobilities (retention Stanford Moore times) 337

25.10: Partial Hydrolysis and End Group Analysis. Acidic hydrolysis of peptides cleave the amide bonds indiscriminately.

Proteases (peptidases): Enzymes that catalyzed the hydrolysis of the amide bonds of peptides and proteins.

Enzymatic cleavage of peptides and proteins at defined sites: • trypsin: cleaves at the C-terminal side of basic residues, Arg, Lys but not His

O R1 O R3 O R1 O R3 H H trypsin H H N N CO2 N N CO2 H N N N H3N N O + H3N 3 H H H O O O O H2O

NH NH3 3 • chymotrypsin: cleaves at the C-terminal side of aromatic residues Phe, Tyr, Trp O R O R O R O R 1 H 3 H 1 H 3 H N N CO2 chymotrypsin N N CO2 H N N N H3N N O + H3N 3 H H H O O O O H2O

338

156 Trypsin and chymotrypsin are endopeptidases

Carboxypeptidase: Cleaves the amide bond of the C-terminal amino acid (exopeptidase)

End Group Analysis. The C-terminal AA is identified by treating with peptide with carboxypeptidase, then analyzing by liquid chormatography (AA Analysis).

N-labeling: The peptide is first treated with 1-fluoro-2,4-dinitro- benzene (Sanger’s reagent), which selectively reacts with the N-terminal amino group. The peptide is then hydrolyzed to their amino acids and the N-terminal amino acid identified as its N-(2,4-dinitrophenyl) derivative (DNP).

NO2 O2N R1 Δ R F H 1 H + N CO2 N CO2 H3N nucleophilic N aromatic H O2N O NO2 O substitution enzymatic O2N digestion R1 plus other unlabeled NH + -or- N 2 amino acids + H 339 H3O , Δ NO2 O

Trypsin: Chymotrypsin: E-A-Y-L-V-C-G-E-R F-V-N-Q-H-L-F F-V-N-Q-H-L-F-S-H-L-K S-H-L-K-E-A-Y G-C-F-L-P-K L-V-C-G-E-R-G-C-F L-G-A L-P-K-L-G-A

F-V-N-Q-H-L-F F-V-N-Q-H-L-F-S-H-L-K S-H-L-K-E-A-Y E-A-Y-L-V-C-G-E-R L-V-C-G-E-R-G-C-F G-C-F-L-P-K L-P-K-L-G-A L-G-A

F-V-N-Q-H-L-F-S-H-L-K-E-A-Y-L-V-C-G-E-R-G-C-F-L-P-K-L-G-A

340

157 25.11: Insulin. Insulin has two peptide chains (the A chain has 21 amino acids and the B chain has 30 amino acids) held together by two disulfide linkages. (please read)

Pepsin: cleaves at the C-terminal side of Phe, Tyr, Leu; but not at Val or Ala.

Pepsin cleavage Trypsin cleavage + H3O cleavage

341

25.12: The Edman Degradation and Automated Peptide . Chemical method for the sequential cleavage and identification of the amino acids of a peptide, one at a time starting from the N-terminus. (Mechanism 25.3, p. 1057) Reagent: Ph-N=C=S, phenylisothiocyanate (PITC)

+ S R S R1 H 1 H pH 9.0 H C N CO Ph N CO2 + H N 2 N N N 2 H H Ph O O H+ H+ Ph N S H N S O N CO H N CO HN 2 Ph + 2 2 HN OH R1 R1 -1 peptide with a new + N-terminal amino acid H (repeat degradation cycle)

Ph N-phenylthiohydantoin: S N O separated by liquid chromatography (based of the R group) and detected HN by UV-vis R1 342

158 Peptide sequencing by Edman degradation: • Cycle the pH to control the cleavage of the N-terminal amino acid by PITC. • Monitor the appearance of the new N-phenylthiohydantoin for each cycle. • Good for peptides up to ~ 25 amino acids long. • Longer peptides and proteins must be cut into smaller fragments before Edman sequencing.

Tandem has largely replaced Edman degradation for peptide sequencing (Fig. 25.9, p. 1058)

343

Epidermal Growth Factor (EGF): the miracle of mother’s spit 53 amino acid, 3 disulfide linkages

H2N-ASN1•SER2•TYR3•PRO4•GLY5•CYS6•PRO7•SER8•SER9•TYR10•! ASP11•GLY12•TYR13•CYS14•LEU15•ASN16•GLY17•GLY18•VAL19•! CYS20•MET21•HIS22•ILE23•GLU24•SER25•LEU26•ASP27•SER28•! TYR29•THR30•CYS31•ASN32•CYS33•VAL34•ILE35•GLY36•TYR37•! SER38•GLY39•ASP40•ARG41•CYS42•GLN43•THR44•ARG45•ASP46•!

LEU47•ARG48•TRP49•TRP50•GLU51•LEU52•ARG53-CO2H! ! Trypsin Chymotrypsin Cyanogen Bromide

1986 Nobel Prize in Medicine or Physiology : 344 Stanley Cohen & Rita Levi-Montalcini

159 25.13: The Strategy for Peptide Synthesis: Chemical synthesis of peptide: 1. Solution phase synthesis 2. Solid-phase synthesis

- H O H - H O 2 H 2 + N CO2H N CO2H H2N H N H N CO H H N CO H 2 2 2 2 2 O O Ala Val Val - Ala Ala - Val (V - A) (A - V) The need for protecting groups O peptide H selectively coupling P N n remove Pn + N OPc Pn OH OPc H N H2N O H - H O O O 2

Ala Val Ala - Val (A - V)

peptide O coupling O O H H H N (-H2O) N N Repeat peptide H N OP Pn N OPc 2 c H synthesis O Ph O Ph P OH Ala - Val n N (A - V) H Phe - Ala - Val O (F - A - V) Phe (F) Orthogonal protecting group strategy: the carboxylate protecting

group must be stable to the reaction conditions for the removal345 of the α-amino protecting group and (vice versa)

25.14: Amino and Carboxyl Group Protection and Deprotection. The α-amino group is protected as a carbamate.

O NH3 O Base O + RO NH RO Cl OH O O O O O

O NH C6H5 O NH O NH

R R O O O tert-butoxycarbonyl benzyloxycarbonyl fluorenylmethylcarbonyl (t-BOC) (cBz) (FMOC) removed with removed with mild acid removed with mild base mild acid or by hydrogenolysis (piperidine)

Protected as a benzyl ester; removed by hydrogenolysis

peptide O O O coupling H mild acid OH + O C6H5 N C6H5 O N H2N C6H5 O N O C6H5 H H O O - H2O O Ph O O H OH N C H O N O O O O H N O C H 6 5 H H H , Pd/C H 2 6 5 H 2 H N N O C6H5 O N N 3 N O O N O C6H5 peptide H H - H2O O O O coupling Ph Ph 346

160 25.15: Formation. Amide formation from the reaction of an amine with a carboxylic acid is slow. Amide bond formation (peptide coupling) can be accelerated if the carboxylic acid is activated. Reagent: dicyclohexylcarbodiimide (DCC) (Mechanism 25.4, p. 1063)

O C6H11 C6H11 O O O H NH NH R O R O R O C R O C + + N N R' H N + H C6H11 NCNC6H11 C H C6H11 C6H11 NCN C6H11 6 11 (DCC) H •• R'-NH2 "activated acid" C H O 6 11 O O NH + R' C6H11 C6H11 R O C R N N N NH H H H HN R' DCU + C6H11 Amide

O O DCC H H cBz N CF3CO2H N cBz OH N OBn H N OBn OBn H 2 N + H2N peptide selectively H O O O O coupling remove N- protecting Ala Val group

DCC O O O O H H H H2, Pd/C Ph N N H2N N cBz N OBn N OH H H cBz OH O O N Ph Ph H 347 O Phe - Ala - Val Phe (F) (F - A - V)

• In order to practically synthesize peptides and proteins, time consuming purifications steps must be avoided until the very end of the synthesis. • Large excesses of reagents are used to drive reactions forward and accelerate the rate of reactions. • How are the excess reagents and by-products from the reaction, which will interfere with subsequent coupling steps, removed without a purification step?

25.16: Solid-Phase Peptide Synthesis: The Merrifield Method. Peptides and proteins up to ~ 100 residues long are synthesized on a solid, insoluble, support. Purification is conveniently accomplished after each step by a simple wash and filtration.

348

161 The solid support (Merrifield resin): polymer

Ph

styrene H3COCH2Cl initiator Ph Ph Ph Ph Ph ZnCl + 2 CH2Cl polymerization Ph Ph Ph Ph Ph Ph

divinylbenzene Ph (crosslinker, ~1 %) Ph

O H _ N O BOC O CF3CO2H R O O O NH NH R BOC 2 R Solid-phase peptide synthesis

FMOC OH purify: purify: N O O O H H wash & filter N wash & filter H2N O N O H H N O DCC FMOC N 2 N O H remove N- H O protecting O Val peptide coupling group

Ph purify: purify by liquid Ph DCC O O H wash & filter N HF chromatograrphy H Ph FMOC N O H N OH N N H2N N H H remove N- remove N- H FMOC OH O O protecting protecting or electrophoresis O O N group and cleave H group O from solid-support Phe (F) 349

Ribonuclease A- 124 amino acids, catalyzes the hydrolysis of RNA Solid-phase synthesis of RNase A:

Synthetic RNase A: 78 % activity 0.4 mg was synthesized 2.9 % overall yield average yield ~ 97% per coupling step His-119 A His-12 A

LYS GLU THR ALA ALA ALA LYS PHE GLU ARG GLN HIS MET ASP SER SER THR SER ALA ALA SER SER SER ASN TYR CYS ASN GLN MET MET LYS SER ARG ASN LEU THR LYS ASP ARG CYS LYS PRO VAL ASN THR PHE VAL HIS GLU SER LEU ALA ASP VAL GLN ALA VAL CYS SER GLN His-12 B LYS ASN VAL ALA CYS LYS ASN GLY GLN THR His-119 B ASN CYS TYR GLN SER TYR SER THR MET SER ILE THR ASP CYS ARG GLU THR GLY SER SER LYS TYR PRO ASN CYS ALA TYR LYS THR THR GLN ALA ASN LYS HIS ILE ILE VAL ALA CYS GLU GLY ASN PRO TYR VAL PRO VAL HIS PHE pdb code: 1AFL ASP ALA SER VAL

R. Bruce Merrifield, Rockefeller University, 1984 Nobel Prize in Chemistry: “for his development of methodology for chemical synthesis on a solid matrix.” 350

162 25.17: Secondary Structures of Peptides and Proteins. β-sheet: Two or more extended peptide chain, in which the amide backbones are associated by hydrogen bonded N → C anti-parallel loop R H O R H O R H O R

or N N N O turn N N N N N → C H O R H O R H O R H O

O H R O H O H R O H

N N N N O N C ← N N N R O H R O H R O H R C ← N parallel N → C O R H O R H O R H O H N → C N N N N N N N O

R H O R H O R H O R crossover O R H O R H O R H O H N N N N N N N O N → C R H O R H O R H O R 351 N → C

α-helix: 3.6 amino acids per coil, 5.4 Å

C 3.6 AA

5.4 Å

N

352

163 myoglobin pdb code: 1WLA

Bacteriorhodopsin pdb code: 1AP9 Anti-parallel β-sheets of lectin Parallel β-sheets pdb code: 2LAL carbonic anhydrase pdb code: 1QRM 353

25.18: Tertiary Structure of Polypeptides and Proteins. Fibrous. Polypeptides strands that “bundle” to form elongated fibrous assemblies; insoluble.

Globular. Proteins that fold into a “spherical” conformation.

Factors that contribute to 3° structure (Table 25.4, p. 1070)

Disulfide bonds between cysteine

Hydrogen bonds

Salt bridges (ion pairs)

Van der Waal forces (hydrophobic effect). Proteins will fold so that hydrophobic amino acids are on the inside (shielded from water) and hydrophilic amino acids are on the outside (exposed to water) 354

164 Enzymes: proteins that catalyze biochemical reactions. • by bringing the reactive atoms together in the optimal geometry for the reaction. • lowering the activation energy (ΔG‡) by stabilizing the transition state and/or high energy intermediate. • many enzymes use the functional groups of the amino acid sidechain to carry out the reactions

Proteases (peptidases): catalyzes the hydrolysis of peptide bonds

O R O R O O R O R O H H protease H H H3N N N H3N N + N N N N CO H O N O H3N N CO H H 2 2 H 2 H O R O R H O R O R Four classes of proteases: Serine (trypsin): aspartate-histidine-serine Aspartyl (HIV protease, renin): two aspartates Cysteine (papain, caspase): histidine-cysteine Metallo (Zn2+) (carboxypeptidase, ACE): glutamate

355

Mechanism of carboxylpeptidase, metalloprotease (Mechanism 25.5, p. 1072) Mechanism of a serine protease (trypsin, chymotrypsin):

oxy-anion hole NH HN O NH HN NH HN O O Ser192O R1 R2 R NHR R1 N 1 2 H Ser H O O 195 acyl- O Ser195 H intermediate H - R2-NH2 H His His 57 N His57 N 57 N

N N N H H H Asp CO - - Asp CO - 102 2 Asp102 CO2 102 2

NH HN O Ser 195 O Ser192O R1 H O RCO H H + 2 H His His57 N 57 N

N N H H - Asp CO - Asp102 CO2 102 2

356

165 25.19: Coenzymes. Some reactions require additional organic or metal ions. These are referred to as cofactors or coenzymes. O H O O NH2 S OH O O O P HO O NH2 P OH P OH NN O O O + HO HO H2N N N NH2 N O C NN NH 2 Thiamin Diphosphate Pyridoxal Phophates Co (vitamin B ) O H (vitamin B1) 6 NN

H2N NH2 H N N N 2 O O N HN N N NH N N O HN H N Fe HO H H - O N N CO2 O -O P O O O CO - O H H HO 2 O Folic Acid OH OH (vitamin B9) Vitamin B12 Heme NH2 (cyanocobalamin) N O N OH O O N HO O P O P O O N - HN NH O- O OH HO OH N NO S CO2H NH N Biotin (vitamin B ) O 7 Flavin Adenine Diphosphate (FAD) (Vitamin B2) 25.20: Protein Quaternary Structure: Hemoglobin. (please read) 25.21: G-Coupled Protein Receptors. (please read) 357

Chapter 26: Nucleosides, , and Nucleic Acids. Nucleic acids are the third class of biopolymers ( and proteins being the others).

Two major classes of nucleic acids deoxyribonucleic acid (DNA): carrier of genetic information ribonucleic acid (RNA): an intermediate in the expression of genetic information and other diverse roles

The Central Dogma (F. Crick):

DNA mRNA Protein (genome) (transcriptome) (proteome)

The monomeric units for nucleic acids are nucleotides. Nucleotides are made up of three structural subunits 1. : ribose in RNA, 2-deoxyribose in DNA 2. Heterocyclic base

3. Phosphodiester 358

166